Abstract

Introduction: Patients with alpha-1 antitrypsin deficiency (AATD) develop pulmonary emphysema prematurely. RAPID, a randomized placebo-controlled trial, showed that treatment with A1-PI (Zemaira/Respreeza) slows emphysema progression. Based on observational data, which showed a reduced loss in forced expiratory volume in one second (FEV1) in a subgroup of patients, current guidelines recommend treatment with A1-PI when FEV1 is between 30 and 65% predicted. However, the relationship between the effect of treatment on lung structure preservation and FEV1 is unclear.

Aim: To assess the effect of treatment in relation to baseline FEV1 % predicted as measured by change in computed tomography (CT) lung density in 180 patients randomized in RAPID with baseline FEV1 between 27 and 79% predicted.

Methods: Changes in annual CT lung density decline rates for both active and placebo treated patients were calculated at 2 years. A random coefficient effect model with baseline FEV1 and treatment group as covariates analyzed the influence on the treatment effect.

Results: Baseline lung function impairment did not affect long-term changes in lung density (p=ns), whereas active treatment was associated with lung density preservation (P<0.0001). The regression line for rate of annual lung density decline vs baseline FEV1% was flat with no interaction between treatment group and baseline FEV1.

Discussion: These data demonstrate that patients with AATD who are treated with A1-PI therapy derive an equal benefit in terms of lung tissue preservation over 2-years that is independent of their pretreatment FEV1%.